Severe Hepatic Steatosis Is Associated With Low-Level Viremia and Advanced Fibrosis in Patients With Chronic Hepatitis B in North America
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SUBMITTER: Ko H
PROVIDER: S-EPMC11307651 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Chronic liver disease (CLD) is associated with tissue-destructive fibrosis. Considering that common mechanisms drive fibrosis across etiologies, and that steatosis is an important cofactor for pathology, we performed RNA sequencing on liver biopsies of patients with different fibrosis stages, resulting from infection with hepatitis C virus (HCV) (with or without steatosis) or fatty liver disease. In combination with enhanced liver fibrosis score correlation analysis, we reveal a common set of genes associated with advanced fibrosis, as exemplified by those encoding the transcription factor ETS-homologous factor (EHF) and the extracellular matrix protein versican (VCAN). We identified 17 fibrosis-associated genes as candidate EHF targets and demonstrated that EHF regulates multiple fibrosis-associated genes, including VCAN, in hepatic stellate cells. Serum VCAN levels were also elevated in advanced fibrosis patients. Comparing biopsies from patients with HCV with or without steatosis, we identified a steatosis-enriched gene set associated with advanced fibrosis, validating follistatin-like protein 1 (FSTL1) as an exemplar of this profile. In patients with advanced fibrosis, serum FSTL1 levels were elevated in those with steatosis (versus those without). Liver Fstl1 mRNA levels were also elevated in murine CLD models. We thus reveal a common gene signature for CLD-associated liver fibrosis and potential biomarkers and/or targets for steatosis-associated liver fibrosis.
| S-EPMC6124454 | biostudies-literature
Project description:Background and aimsChronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV.Approach and resultsWe included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200 IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]).ConclusionIndividuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.
| S-EPMC8843101 | biostudies-literature
Project description:To determine whether chemotherapy treatment at least 6 months prior to the detection of hepatic steatosis is associated with advanced hepatic fibrosis. Demographics, comorbid conditions, and laboratory data for cancer patients with hepatic steatosis were reviewed. The primary end point of this study was a low probability of fibrosis as calculated by the AST-to-platelet ratio index (APRI)-a surrogate for the absence of histologic bridging fibrosis and/or cirrhosis. Of 279 patients, 117 (41.9 %) were treated with chemotherapy and 197 (66.3 %) had a low probability of fibrosis by APRI. A smaller proportion of patients treated with chemotherapy had a low probability of hepatic fibrosis compared with untreated patients (64.1 vs. 75.3 %, p = 0.04). On multivariable analysis, chemotherapy treatment was a negative predictive factor for a low probability of fibrosis (OR 0.366 [95 % CI 0.184-0.708], p < 0.01). Among chemotherapy-treated patients, 75 (64.1 %) had a low probability of fibrosis. There were no differences in chemotherapy duration (mean 7.8 vs. 7.5 cycles) and interval from last dose to steatosis diagnosis (24.3 vs. 21.4 months) between patients with and without a low probability of fibrosis. A smaller proportion of patients treated with irinotecan or 5-fluorouracil had a low probability of fibrosis (37.3 vs. 66.7 %, p = 0.04). On multivariable analysis, irinotecan or 5-fluorouracil treatment was a negative predictive factor for low probability of fibrosis (OR 0.277 [95 % CI 0.091-0.779], p = 0.02). Prior chemotherapy treatment, especially with 5-fluorouracil or irinotecan, is a negative predictor for the absence of advanced hepatic fibrosis among patients with steatosis.
| S-EPMC4419370 | biostudies-literature
Project description:PurposeThe effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard.MethodsBetween February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness.ResultsAC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively).ConclusionAC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.
| S-EPMC10915114 | biostudies-literature
Project description:Background/aimsThe recognition of a correlation between patatin-like phospholipase domain containing-protein 3 (PNPLA3) rs738409 (C>G) and the severity of liver steatosis or fibrosis in chronic hepatitis C (CHC) has not reached a consensus. This meta-analysis sought to investigate with accuracy the association between the PNPLA3 rs738409 (C>G) polymorphism and liver steatosis and advanced fibrosis in CHC patients.MethodsWe performed a comprehensive literature search from the PubMed, Embase, Web of Science, and Google Scholar databases up to December 31, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using Stata 12.0 software.ResultsThe meta-analysis revealed the severity of liver fibrosis was significantly higher in CHC patients with PNPLA3 rs738409 GG in Caucasians (versus CC+CG OR, 2.29; 95% CI, 1.57 to 3.35; p<0.05) but not Asian populations. In Caucasians, liver steatosis was also more severe in CHC patients with rs738409 GG (versus CC+CG; OR, 4.33; 95% CI, 2.59 to 7.22; p<0.05). The sensitivity analysis indicated the results of this meta-analysis were stable and no publication bias was detected.ConclusionsPNPLA3 rs738409 (C>G) was associated with the risk of both advanced liver fibrosis and steatosis in patients with CHC, especially among Caucasian populations.
| S-EPMC4849700 | biostudies-literature
Project description:Background & aimLiver fibrosis is associated with poor patient-reported outcomes (PROs), but the impact of steatosis is unknown. We aimed to evaluate the impact of steatosis on PROs independent of liver fibrosis.MethodsWe evaluated the impact of steatosis, measured by Controlled-Attenuation Parameter (CAP) on transient elastography, and PROs using the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database. We used univariate and multivariate logistic and ordinal regression to evaluate categorical CAP score with PROs measuring physical disability, general health and depression.ResultsOf 4,509 participants included, 38% had severe steatosis (> 280 dB/m). Those with severe steatosis were older and more likely to be male (56% vs. 43% and 51%). On univariate analysis, severe steatosis was associated with more difficulty walking (P = 0.01), dressing (P = 0.005), lifting objects (P = 0.02), bending (P < 0.001), and moving large objects (P = 0.0006). After multivariate adjustment, severe steatosis remained associated with difficulty lifting objects (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.2-2.4, P = 0.01) and difficulty bending (OR: 1.8, 95% CI: 1.2-2.7, P = 0.006). Severe steatosis increased risk of having any of the disabilities (OR: 1.7, 95% CI: 1.2-2.4, P = 0.008) and had higher ordinal disability index (OR: 1.6, 95% CI: 1.2-2.2, P = 0.007). Lastly, severe steatosis was also associated with worse self-perceived health status (OR: 1.5, 95% CI: 1.2-1.9, P = 0.002), while general health compared to one year ago and depression trended toward significance.ConclusionPatients with severe steatosis are at increased risk of physical disability and have worse self-perceived health status independent of liver fibrosis.
| S-EPMC10697075 | biostudies-literature
Project description:IntroductionFatty liver disease (FLD) influences liver disease progression and liver cancer risk. We investigated the impact of FLD on liver disease severity in a large North American cohort with chronic hepatitis B virus (HBV).MethodsLiver biopsies from 420 hepatitis B surface antigen-positive adults enrolled in the Hepatitis B Research Network and who were not on HBV therapy in the previous month were evaluated for inflammation and fibrosis. Steatohepatitis was based on steatosis, hepatocyte ballooning ± Mallory-Denk bodies, and perisinusoidal fibrosis. Models evaluated factors associated with steatohepatitis, and the associations of steatohepatitis with fibrosis, and longitudinal alanine aminotransferase, aspartate aminotransferase, and Fibrosis-4.ResultsThe median age was 42 years, 62.5% were male, and 79.5% were Asian. One hundred thirty-two (31.4%) patients had FLD (77 [18.3%] steatosis only, 55 [13.1%] steatohepatitis). Older age, overweight/obesity, and diabetes were associated with steatohepatitis. Steatohepatitis (vs no FLD) was associated with 1.68 times higher risk of advanced fibrosis at baseline (95% confidence interval, 1.12-2.51), and there was an indication of higher incident cirrhosis rate during follow-up. Steatohepatitis vs no FLD was also independently associated with, on average, 1.39 times higher alanine aminotransferase (P < 0.01) and 1.25 times higher Fibrosis-4 (P = 0.04) across 4 years.DiscussionCoexisting steatosis occurred in nearly a third of adults (13% had steatohepatitis) with chronic HBV in this North American cohort who underwent liver biopsies. Steatohepatitis was associated with advanced fibrosis and higher biochemical measures of hepatic inflammation over time. Therefore, in addition to viral suppression, screening for and managing metabolic abnormalities is important to prevent disease progression in HBV.
| S-EPMC8484018 | biostudies-literature
Project description:BackgroundMetabolic syndrome (MetS) is a group of factors associated with increased risks of cardiovascular disease and overall mortality. Nonalcoholic fatty liver disease (NAFLD) is a common disorder that has been shown to cause hepatic steatosis and fibrosis. The relationship between NAFLD and MetS appears to be bidirectional, but very few studies have examined the role of MetS in hepatic steatosis and fibrosis. The present study investigated the relationships between MetS and its components and the severity of hepatic fibrosis and steatosis, and fibrosis independent of steatosis.MethodsThe study was a cross-sectional population-based survey of 4,678 National Health and Nutrition Examination Survey participants from 2017 to 2018 in the United States. Hepatic fibrosis and steatosis were measured using liver elastography. The MetS components were assessed using demographic, examination, laboratory, and self-reported data.ResultsUsing survey-weighted population estimates, 26% of the population had steatosis, 7.5% had fibrosis, and 3.3% had fibrosis without steatosis. The adjusted odds ratio for any level of steatosis was 4.12 times higher (95% confidence interval [CI], 3.16-5.37) and any level of fibrosis was 3.34 times higher (95% CI, 2.26-4.94) among participants with MetS than those without. The adjusted odds ratio for fibrosis without steatosis is 2.67 times higher (95% CI, 1.47-4.87) among participants with MetS than those without.ConclusionThe presence of MetS significantly increases the risk of hepatic fibrosis and steatosis, providing evidence for MetS to be considered an additional independent risk factor for hepatic fibrosis together with other known etiologies.
| S-EPMC8987451 | biostudies-literature
Project description:INTRODUCTION:Patients with hepatitis B early antigen (HBeAg)-negative chronic hepatitis B (CHB) and low-level viremia are a heterogeneous group. Identifying those at risk of developing active CHB requiring antiviral therapy is important. In this study, we prospectively characterize incidence rates and predictors of transitioning from inactive to active CHB in a North American adult cohort. METHODS:Participants in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B Research Network cohort who were HBeAg negative with baseline hepatitis B virus (HBV) DNA ≤ 10,000 IU/mL were included in the study. Cox regression models were used to estimate the proportion of individuals in 3 baseline HBV DNA categories (≤100, 101 to ≤2,000, and 2,001 to ≤10,000 IU/mL) who developed phase transition defined by HBV DNA > 10,000 IU/mL and alanine aminotransferase (ALT) > 2× upper limit of normal or initiated treatment during follow-up. RESULTS:Of 970 participants meeting inclusion criteria, 15% experienced phase transition or initiated treatment over a median follow-up of 4 years: 9% of those with baseline HBV DNA ≤ 100 IU/mL, 14% with HBV DNA 101 to ≤2,000 IU/mL, and 24% with HBV DNA 2,001 to ≤10,000 IU/mL (P < 0.001). The overall rate of phase transition or treatment initiation was 7.6 per 100 person-years: 4.6 in those with HBV DNA ≤ 100 IU/mL, 6.8 in those with HBV DNA 101 to ≤2,000 IU/mL, and 12.2 in those with HBV DNA 2,001 to ≤10,000 IU/mL (P < 0.001). Factors independently associated with higher rate of phase transition or treatment initiation included HBV genotype B or C, higher baseline ALT and HBV DNA levels, lower platelet count, quantitative hepatitis B surface antigen > 1,000 IU/mL, and hyperlipidemia. Only higher ALT, higher HBV DNA, and lower platelets were associated with phase transition when patients starting treatment were censored. DISCUSSION:Most adults in this North American cohort with HBeAg-negative CHB and low-level viremia remained inactive and off treatment over 4 years. Transition from inactive to active CHB is infrequent and predominantly associated with viral rather than host factors.
| S-EPMC6832838 | biostudies-literature
Project description: Not available
| S-EPMC10851070 | biostudies-literature